Objective To investigate the clinical value of tumor-stroma ratio (TSR) in combination with KRAS, BRAF, NRAS, and microsatellite status for prognostic assessment of patients with colorectal cancer. Methods A total of 51 colorectal cancer cases meeting the inclusion and exclusion criteria were enrolled in this study. TSR levels were evaluated through optical microscopy. The KRAS/NRAS/BRAF mutation profiles and microsatellite status were determined in accordance with genetic testing results. Clinical data, pathological characteristics, and survival outcomes were systematically recorded. Results Among the 51 patients with colorectal cancer, 19 (37.3%) were categorized into the low stromal group and 32 (62.7%) into the high stromal group. Statistically significant differences were observed between the two groups in drug resistance, M stage, TNM stage, neural invasion, and microsatellite status (P<0.05). Compared with patients exhibiting high TSR, those with low TSR demonstrated significantly increased recurrence rates (5 vs. 21 cases, P=0.007), shortened disease-free survival (34.21 vs. 14.34 months, P=0.001), and reduced overall survival (38.79 vs. 23.09 months, P=0.021). Multivariate Cox regression analysis identified N stage, M stage, TNM stage, neural invasion, lymphovascular invasion, and TSR as independent risk factors for disease-free survival. N stage, M stage, neural invasion, lymphovascular invasion, and TSR emerged as independent prognostic factors for overall survival (P<0.05). Although the combined models of TSR with KRAS, NRAS, BRAF, and microsatellite status, respectively, demonstrated overall statistical significance (P<0.05), none of the dummy variables in these models reached individually statistical significance (P>0.05), and therefore cannot be considered independent prognostic factors. Conclusion TSR serves as an independent predictor of poor prognosis in advanced colorectal cancer, with patients exhibiting low TSR demonstrating a significantly higher risk of recurrence and metastasis than those with high TSR. For patients with colon cancer undergoing first-line palliative chemotherapy after postoperative recurrence, histopathological assessment of TSR in primary tumor sites holds prognostic value and may serve as a relevant factor for evaluating treatment resistance in clinical management.

AIM:To establish a stable and efficient rat model of alcoholic liver disease(ALD),we investigat-ed the effects of different alcoholic beverage concentrations and alcohol dosing regimens.METHODS:(1)SPF-grade male SD rats were randomized into 5 groups(n=10):blank,ALD1,ALD2,ALD3,and ALD4.Except for the blank group,rats received intragastric administration of 56%alcohol(6 mL/kg twice daily with an 8-hour interval)for 4 weeks,along with free access to 0%,5%,10%,or 15%alcoholic beverage to evaluate concentration-dependent effects.(2)An-other cohort was divided into three groups(n=10):blank,ALD5,and ALD6.Rats(except blank)were gavaged with 56%alcohol twice daily for 9 weeks(8 mL/kg for ALD5;6 mL/kg in week 1,increasing by 0.5 mL/kg weekly for ALD6),with 10%alcoholic beverage available ad libitum to assess dose-dependent effects.Serum biochemical markers[alanine aminotransferase(ALT),aspartate aminotransferase(AST),total cholesterol(TC),triglycerides(TG),high-density li-poprotein cholesterol(HDL-C),and low-density lipoprotein cholesterol(LDL-C)]and inflammatory cytokines[interleu-kin-6(IL-6),IL-1β and tumor necrosis factor-α(TNF-α)]were analyzed after modeling,complemented by imaging(B-ultrasound,CT,and MRI).Success and survival rates were calculated.RESULTS:(1)ALD1～4 groups exhibited sig-nificantly elevated ALT,AST,TC,TG,LDL-C,IL-1β,IL-6 and TNF-α(P<0.05 or P<0.01)and reduced HDL-C and liver-to-spleen CT density ratio vs blank.ALD3(10%alcoholic beverage)showed the highest modeling success rate with low mortality.(2)ALD5 and ALD6 groups also had siginificant differin terms(P<0.01),with ALD6(gradually increas-ing dose)displaying more severe liver injury,higher success rate,and better survival.CONCLUSION:The optimal ALD model was induced by intragastric administration of 56%alcohol(6 mL/kg twice daily in week 1,increasing by 0.5 mL/kg weekly for 9 weeks)combined with 10%alcoholic beverage.This protocol offers a reliable approach for ALD re-search and drug development.

Objective:To investigate the efficacy of anatomical resection (AR) in the early stages of treating solitary hepatocellular carcinoma (HCC) combined with liver cirrhosis with a diameter of ≤5 cm in comparison to different surgical methods of preferential hepatic parenchymal preservation (non-anatomical liver resection, NAR).Methods:The clinical data of 1 390 cases with solitary HCC combined with liver cirrhosis at an early stage who underwent liver resection at Mengchao Hepatobiliary Hospital of Fujian Medical University and six other medical centers from September 2013 to May 2019 were retrospectively analyzed. Patients were divided into the AR group (486 cases) and the NAR group (904 cases) and the wide surgical margin (WSM) group (745 cases) and the narrow surgical margin (NSM) group (645 cases) according to whether they received AR and the width of the surgical margin (1 cm). The basic information of the patients, preoperative evaluation index data, and postoperative follow-up (follow-up every 3 months) were collected. The Kaplan-Meier method was used to plot the survival curve.The log-rank test was used to compare the difference in survival between the two groups. The Cox proportional hazards regression model was used to analyze the factors affecting the prognosis. Propensity score matching (PSM) was applied to reduce intergroup bias.Results:The overall survival (OS) rates for all patients at 1, 3, and 5 years were 95.5%, 79.9%, and 63.5%, respectively. The recurrence-free survival (RFS) rates were 81.5%, 59.0%, and 43.7%, respectively. There was a statistically significant difference in RFS rate between the AR group and the NAR group prior to PSM, but no statistically significant difference in OS rate (RFS rate: 47.0% vs. 41.9%, P<0.05; OS rate: 64.4% vs. 62.9%, P>0.05). The postoperative RFS rate and OS rate were significantly superior in the WSM group than those of the NSM group (RFS rate: 47.8% vs. 37.2%, P<0.001; OS rate: 69.0% vs. 57.3%, P<0.001). There was no statistically significant difference in OS rate and RFS rate between the AR group and the NAR group following PSM (RFS: 46.3% vs. 45.1%, P>0.05; OS rate: 64.0% vs. 64.3%, P>0.05).The 5-year OS and RFS rates in the WSM group were 66.8% and 60.2%, respectively. The 5-year OS and RFS rates for the NSM group were 48.7% and 41.4%, respectively, with a statistically significant difference ( P<0.05). Cox multivariate analysis indicated that serum albumin, tumor diameter, microvascular invasion, and surgical margin were independent prognostic factors affecting OS and RFS. The Child-Pugh grade and satellite lesions were independent prognostic factors affecting OS. Conclusion:Anatomical liver resection is not an independent risk factor for prognosis, but the state of the resection margin determines the prognosis of patients with solitary HCC combined with cirrhosis. Therefore, hepatic resection margins should be prioritized in such patients.

AIM:To establish a stable and efficient rat model of alcoholic liver disease(ALD),we investigat-ed the effects of different alcoholic beverage concentrations and alcohol dosing regimens.METHODS:(1)SPF-grade male SD rats were randomized into 5 groups(n=10):blank,ALD1,ALD2,ALD3,and ALD4.Except for the blank group,rats received intragastric administration of 56%alcohol(6 mL/kg twice daily with an 8-hour interval)for 4 weeks,along with free access to 0%,5%,10%,or 15%alcoholic beverage to evaluate concentration-dependent effects.(2)An-other cohort was divided into three groups(n=10):blank,ALD5,and ALD6.Rats(except blank)were gavaged with 56%alcohol twice daily for 9 weeks(8 mL/kg for ALD5;6 mL/kg in week 1,increasing by 0.5 mL/kg weekly for ALD6),with 10%alcoholic beverage available ad libitum to assess dose-dependent effects.Serum biochemical markers[alanine aminotransferase(ALT),aspartate aminotransferase(AST),total cholesterol(TC),triglycerides(TG),high-density li-poprotein cholesterol(HDL-C),and low-density lipoprotein cholesterol(LDL-C)]and inflammatory cytokines[interleu-kin-6(IL-6),IL-1β and tumor necrosis factor-α(TNF-α)]were analyzed after modeling,complemented by imaging(B-ultrasound,CT,and MRI).Success and survival rates were calculated.RESULTS:(1)ALD1～4 groups exhibited sig-nificantly elevated ALT,AST,TC,TG,LDL-C,IL-1β,IL-6 and TNF-α(P<0.05 or P<0.01)and reduced HDL-C and liver-to-spleen CT density ratio vs blank.ALD3(10%alcoholic beverage)showed the highest modeling success rate with low mortality.(2)ALD5 and ALD6 groups also had siginificant differin terms(P<0.01),with ALD6(gradually increas-ing dose)displaying more severe liver injury,higher success rate,and better survival.CONCLUSION:The optimal ALD model was induced by intragastric administration of 56%alcohol(6 mL/kg twice daily in week 1,increasing by 0.5 mL/kg weekly for 9 weeks)combined with 10%alcoholic beverage.This protocol offers a reliable approach for ALD re-search and drug development.

Objective:To investigate the efficacy of anatomical resection (AR) in the early stages of treating solitary hepatocellular carcinoma (HCC) combined with liver cirrhosis with a diameter of ≤5 cm in comparison to different surgical methods of preferential hepatic parenchymal preservation (non-anatomical liver resection, NAR).Methods:The clinical data of 1 390 cases with solitary HCC combined with liver cirrhosis at an early stage who underwent liver resection at Mengchao Hepatobiliary Hospital of Fujian Medical University and six other medical centers from September 2013 to May 2019 were retrospectively analyzed. Patients were divided into the AR group (486 cases) and the NAR group (904 cases) and the wide surgical margin (WSM) group (745 cases) and the narrow surgical margin (NSM) group (645 cases) according to whether they received AR and the width of the surgical margin (1 cm). The basic information of the patients, preoperative evaluation index data, and postoperative follow-up (follow-up every 3 months) were collected. The Kaplan-Meier method was used to plot the survival curve.The log-rank test was used to compare the difference in survival between the two groups. The Cox proportional hazards regression model was used to analyze the factors affecting the prognosis. Propensity score matching (PSM) was applied to reduce intergroup bias.Results:The overall survival (OS) rates for all patients at 1, 3, and 5 years were 95.5%, 79.9%, and 63.5%, respectively. The recurrence-free survival (RFS) rates were 81.5%, 59.0%, and 43.7%, respectively. There was a statistically significant difference in RFS rate between the AR group and the NAR group prior to PSM, but no statistically significant difference in OS rate (RFS rate: 47.0% vs. 41.9%, P<0.05; OS rate: 64.4% vs. 62.9%, P>0.05). The postoperative RFS rate and OS rate were significantly superior in the WSM group than those of the NSM group (RFS rate: 47.8% vs. 37.2%, P<0.001; OS rate: 69.0% vs. 57.3%, P<0.001). There was no statistically significant difference in OS rate and RFS rate between the AR group and the NAR group following PSM (RFS: 46.3% vs. 45.1%, P>0.05; OS rate: 64.0% vs. 64.3%, P>0.05).The 5-year OS and RFS rates in the WSM group were 66.8% and 60.2%, respectively. The 5-year OS and RFS rates for the NSM group were 48.7% and 41.4%, respectively, with a statistically significant difference ( P<0.05). Cox multivariate analysis indicated that serum albumin, tumor diameter, microvascular invasion, and surgical margin were independent prognostic factors affecting OS and RFS. The Child-Pugh grade and satellite lesions were independent prognostic factors affecting OS. Conclusion:Anatomical liver resection is not an independent risk factor for prognosis, but the state of the resection margin determines the prognosis of patients with solitary HCC combined with cirrhosis. Therefore, hepatic resection margins should be prioritized in such patients.

Objective:To investigate the evaluation efficacy and predictive prognostic value of alpha-fetoprotein (AFP) response in tyrosine kinase inhibitors (TKIs) in combination with PD-1 inhibitors (α-PD-1) for intermediate-to-advanced hepatocellular carcinoma (HCC).Methods:The retrospective cohort study was conducted. The clinicopathological data of 205 patients with intermediate-to-advanced HCC who were admitted to 9 medical centers, including Mengchao Hepatobiliary Hospital of Fujian Medical University et al, from March 2020 to July 2022 were collected. There were 178 males and 27 females, aged (52±12)years. Based on AFP response at 6-8 weeks after treatment, patients were divided into the AFP response group (AFP level decreased by ≥50% compared to baseline) and the AFP no response group (AFP level decreased by <50% compared to baseline). Observation indicators: (1) AFP response evaluation of anti-tumor efficacy; (2) comparison of patient prognosis; (3) analysis of factors affecting patient prognosis. Measurement data with normal distrubution were represented as Mean± SD, and measurement data with skewed distribution were represented as M(range) and M( Q1, Q3). Count data were described as absolute numbers, and comparison between groups was conducted using the chi-square test. The Kaplan-Meier method was used to draw survival curve and calculate survival rate, and the Log-Rank test was used for survival analysis. The COX proportional risk model was used for univariate analysis and the COX stepwise regression model was used for multivariate analysis. Results:(1) AFP response evaluation of anti-tumor efficacy. Before treatment, all 205 patients were positive of AFP, with a baseline AFP level of 1 560(219,3 400)μg/L. All 205 patients were treated with TKIs in combination with α-PD-1, and the AFP level was 776(66,2 000)μg/L after 6 to 8 weeks of treatment. Of the 205 patients, 88 cases were classified as AFP response and 117 cases were classified as AFP no response. According to the response evaluation criteria in solid tumors version 1.1, the objective response rate (ORR) and disease control rate (DCR) were 42.05%(37/88) and 94.32%(83/88) in patients of the AFP response group and 16.24% (19/117) and 64.10% (75/117) in patients of the AFP no response group, showing significant differences between them ( χ2=16.846, 25.950, P<0.05). According to the modified response evaluation criteria in solid tumors, the ORR and DCR were 69.32% (61/88) and 94.32% (83/88) in patients of the AFP response group and 33.33% (39/117) and 64.10% (75/117) in patients of the AFP no response group, showing significant differences between them ( χ2=26.030, 25.950, P<0.05). (2) Comparison of patient prognosis. All 205 patients were followed up for 12.4(range, 2.4-34.0)months after treatment. The median progression free survival time and total survival time were 5.5 months and 17.8 months, respectively. The 1-year, 2-year progression free survival rates were 20.8% and 7.2%, and the 1-year, 2-year overall survival rates were 68.7% and 31.5%, respectively. The median progression free survival time, 1-year and 2-year progression free survival rates were 9.7 months, 39.6% and 14.2% in patients of the AFP response group and 3.7 months, 7.8% and 2.0% in patients of the AFP no response group, showing a significant difference in progression free survival between them ( χ2=43.154, P<0.05). The median overall survival time, 1-year and 2-year overall survival rates were not reached, 85.2% and 56.3% in patients of the AFP response group and 14.6 months, 56.3% and 14.5% in patients of the AFP no response group, showing a significant difference in overall survival between them ( χ2=33.899, P<0.05). (3) Analysis of factors affecting patient prognosis. Results of multivariate analysis showed that invasion of large blood vessels, extrahepatic metastasis, combined hepatic artery intervention therapy, and AFP response were independent factors influencing progression free survival in patients with intermediate-to-advanced HCC who were treated with TKIs in combination with α-PD-1 ( hazard ratio=1.474, 1.584, 0.631, 0.367, 95% confidence interval as 1.069-2.033, 1.159-2.167, 0.446-0.893, 0.261-0.516, P<0.05), and Eastern Cooperative Oncology Group score, invasion of large blood vessels, extrahepatic metastasis, and AFP response were independent factors influencing overall survival in patients with intermediate-to-advanced HCC who were treated with TKIs in combination with α-PD-1 ( hazard ratio= 1.347, 1.914, 1.673, 0.312, 95% confidence interval as 1.041-1.742, 1.293-2.833, 1.141-2.454, 0.197-0.492, P<0.05). Conclusions:AFP response at 6-8 weeks after treatment can effectively evaluate anti-tumor efficacy of TKIs in combination with α-PD-1 for intermediate-to-advanced HCC. AFP response is the independent factor influencing progression free survival and overall survival in patients with intermediate-to-advanced HCC who were treated with TKIs in combination with α-PD-1.

Diabetes mellitus(DM)is a disease syndrome characterized by chronic hyperglycaemia.A long-term high-glucose environment leads to reactive oxygen species(ROS)production and nuclear DNA damage.Human umbilical cord mesenchymal stem cell(HUcMSC)infusion induces significant antidiabetic effects in type 2 diabetes mellitus(T2DM)rats.Insulin-like growth factor 1(IGF1)receptor(IGF1R)is important in promoting glucose metabolism in diabetes;however,the mechanism by which HUcMSC can treat diabetes through IGF1R and DNA damage repair remains unclear.In this study,a DM rat model was induced with high-fat diet feeding and streptozotocin(STZ)administration and rats were infused four times with HUcMSC.Blood glucose,interleukin-6(IL-6),IL-10,glomerular basement membrane,and renal function were examined.Proteins that interacted with IGF1R were determined through coimmunoprecipitation assays.The expression of IGF1R,phosphorylated checkpoint kinase 2(p-CHK2),and phosphorylated protein 53(p-p53)was examined using immunohistochemistry(IHC)and western blot analysis.Enzyme-linked immunosorbent assay(ELISA)was used to determine the serum levels of 8-hydroxydeoxyguanosine(8-OHdG).Flow cytometry experiments were used to detect the surface markers of HUcMSC.The identification of the morphology and phenotype of HUcMSC was performed by way of oil red"O"staining and Alizarin red staining.DM rats exhibited abnormal blood glucose and IL-6/10 levels and renal function changes in the glomerular basement membrane,increased the expression of IGF1 and IGF1R.IGF1R interacted with CHK2,and the expression of p-CHK2 was significantly decreased in IGF1R-knockdown cells.When cisplatin was used to induce DNA damage,the expression of p-CHK2 was higher than that in the IGF1R-knockdown group without cisplatin treatment.HUcMSC infusion ameliorated abnormalities and preserved kidney structure and function in DM rats.The expression of IGF1,IGF1R,p-CHK2,and p-p53,and the level of 8-OHdG in the DM group increased significantly compared with those in the control group,and decreased after HUcMSC treatment.Our results suggested that IGF1R could interact with CHK2 and mediate DNA damage.HUcMSC infusion protected against kidney injury in DM rats.The underlying mechanisms may include HUcMSC-mediated enhancement of diabetes treatment via the IGF1R-CHK2-p53 signalling pathway.

Objective:To investigate the advantages of Da Vinci robotic thyroidectomy in treatment of the unilateral papillary thyroid microcarcinoma (PTMC).Methods:The clinical data of 49 patients with unilateral thyroid cancer admitted to the First Hospital of Shanxi Medical University from June 2018 to March 2020 were retrospectively analyzed, and they were divided into Da Vinci robotic group (the experimental group, 18 cases) and conventional surgery group (the control group, 31 cases) according to the surgical method. The clinicopathological characteristics, perioperative and postoperative related indexes changes, length of hospital stay, incidence of surgical complications, and operation cost of both groups of patients were analyzed. Visual analogue scale (VAS) was used to evaluate postoperative pain.Results:There were statistically significant differences in age, marriage and education background of both groups (all P < 0.05). There were statistically significant differences in the number of central lymph node dissection [(4.3±2.0) vs. (6.5±3.9)], operation time [198.5 min (166.3 min, 228.5 min) vs. 82.0 min (60.0 min, 102.0 min)], pain score of 24 h after surgery [3 scores (3 scores, 4 scores) vs. 2 scores (2 scores, 3 scores)], postoperative total drainage volume [49.0 ml (40.8 ml, 56.5 ml) vs. 37.0 ml, (29.0 ml, 44.0 ml)], operation cost [33,200 yuan (33,100 yuan, 34,000 yuan) vs. 5,200 yuan (4,200 yuan, 5,900 yuan)], and differences were statistically significant (all P < 0.05). No postoperative complications such as hemorrhage, fat liquefaction and subcutaneous ecchymosis occurred in all patients of the two groups. Conclusion:Da Vinci robotic thyroidectomy is safe and reliable in treatment of the unilateral PTMC, and it has good therapeutic effects.

Objective To investigate the effect of general anesthesia combined with epidural block anesthesia on intestinal barrier function in patients with gastric cancer after radical resection.Methods 90 patients with gastric cancer undergoing laparoscopic radical resection were selected.They were randomly divided into observation group (epidural anesthesia plus general anesthesia) and control group (general anesthesia),45 cases in each group.The intraoperative blood loss,intraoperative infusion volume,postoperative exhaust time,postoperative complications and the function of intestinal barrier effects were compared between the two groups.Results The total incidence rate of postoperative complications in the observation group(8.89％) was significantly lower than that in the control group (28.89％) (x2 =4.83,P ＜ 0.05).The hospital stay in the observation group [(12.5 ± 4.23) d] was significantly shorter than that in the control group [(17.5 ± 5.26) d] (t =3.27,P ＜ 0.05).The two amine oxidase [(3.88 ± 0.98) U/L],D-lactic acid [(7.44 ± 5.23) mg/L],endotoxin [(13.44 ± 2.12) U/L] levels of the observation group were significantly lower than those of the control group [two amine oxidase (11.33 ± 1.25) U/L,D-lactic acid (15.34 ±3.21) mg/L,endotoxin (21.03 ± 0.82) U/L] (t =5.63,5.02,4.19,all P ＜ 0.05).Conclusion Compared with total intravenous anesthesia,total intravenous anesthesia combined with epidural anesthesia is beneficial to the recovery of intestinal barrier function after radical gastrectomy,and can shorten the postoperative hospital stay.It is worthy of clinical application and popularization.

Objective To systematically review the prognostic factors of intrahepatic cholangiocarcinoma (ICC) and clinical significance of abdominal lymphadenectomy.Methods PubMed was queried with the terms of intrahepatic cholangiocarcinoma,survival,surgery,lymph or vascular invasion to find all studies published from January 2005 to December 2015.Authors were contacted by letters for the publications that were initially ineligible due to insufficient information for data extraction,responses were received,so these publications were included.Data were analyzed and evaluated by 2 independent researchers.Prognostic factors of ICC (vascular invasion,bile duct invasion,lymphatic vessel invasion,lymph node metastasis and peripheral nerve invasion) and related-factors of surgical method (R0 resection and lymph node dissected) were analyzed.The 3-,5-year survival rate,tumor-free survival rate and effect of lymph node dissected for prognosis of patients were extracted.Heterogeneity was analyzed by the chi-squared test and I2 test.The hazard ratio (HR) and 95％ confidence interval (CI) were transformed to Log (HR) and standard errors (SE) Log (HR).HR and 95％ CI of clinical factors associated with outcomes were done using univariate COX regression models.Publication bias was evaluated by the Egger's method,visualizing with funnel plot.Results A total of 48 publications including 7 868 patients with ICC were eligible to be included in this analysis,12 of 48 publications were included in the Mata analysis.Of 7 868 patients with ICC,vascular invasion,bile duct invasion,lymphatic vessel invasion,lymph node metastasis,peripheral nerve invasion,R0 resection and lymph node dissected were detected in 30％ (5％-98％),40％ (11％-59％),45％ (35％-65％),28％ (9％-100％),25％ (7％-55％),79％ (35％-100％) and 64％ (9％-100％),respectively.The 3-,5-year survival rate and 3-,5-year tumor-free survival rate were 39％ (16％-65％),29％(5％-60％) and 34％ (3％-60％),23％ (0-52％),respectively.The results of meta-analysis showed that lymph node metastasis and vascular invasion were factors affecting the prognosis of patients with ICC (HR =2.30,1.92,95 ％ CI:1.94-2.73,1.64-2.25,P ＜ O.05).Among the patients without lymph node metastasis,5-year survival rate in patients with and without lymphadenectomy was 17％-64％ and 15％-64％,respectively,showing no statistically significant difference (P ＞ 0.05).Among the patients with lymph node metastasis,5-year survival rate in patients with and without lymphadenectomy was 48％ and 11％,respectively,showing a statistically significant difference (P＜0.05).Conclusions Lymph node metastasis and vascular invasion are the risk factors affecting the prognosis of patients with ICC.Routine lymphadenectomy for ICC cannot show survival benefit,while routine lymphadenectomy should be applied to patients with ICC and uncertain lymph node metastasis.